ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2010
Local low-dose lovastatin delivery improves the bone-healing defect caused by Nf1 loss of function in osteoblasts.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis.BMC musculoskeletal disorders · 2024Pooled it
- Neurofibromin in bone disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- MEK-SHP2 inhibition prevents tibial pseudarthrosis caused byScience translational medicine · 2024Article
- Statins in Children with Neurofibromatosis Type 1: A Systematic Review of Randomized Controlled Trials.Children (Basel, Switzerland) · 2023Review
- Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice.The Journal of clinical investigation · 2023Article
- Identifying Bone Matrix Impairments in a Mouse Model of Neurofibromatosis Type 1 (NF1) by Clinically Translatable Techniques.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- A novel mutation in NF1 gene of patient with Neurofibromatosis type 1: A case report and functional study.Molecular genetics & genomic medicine · 2021Article
- Coordinated medical care for children with neurofibromatosis type 1 and related RASopathies in Poland.Archives of medical science : AMS · 2021Article
- Characterization of Two Loss-of-Function NF1 Variants in Chinese Patients and Potential Molecular Interpretations of Phenotypes.Frontiers in genetics · 2021Article
- Atorvastatin promotes bone formation in aged apoEJournal of orthopaedic surgery and research · 2020Article
- Comparative impact of systemic delivery of atorvastatin, simvastatin, and lovastatin on bone mineral density of the ovariectomized rats.Endocrine · 2018Article
- Article
- Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans.Free radical biology & medicine · 2016Article
- Combined MEK inhibition and BMP2 treatment promotes osteoblast differentiation and bone healing in Nf1Osx -/- mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Article
- Article
- Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1.Nature medicine · 2014Article
- Article
- Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in neurofibromin-deficient mice.Human molecular genetics · 2013Article
- Hyperactive transforming growth factor-β1 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Delayed fracture healing in tetranectin-deficient mice.Journal of bone and mineral metabolism · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Postfracture tibial nonunion (pseudoarthrosis) leads to lifelong disability in patients with neurofibromatosis type I (NF1), a disorder caused by mutations in the NF1 gene. To determine the contribution of NF1 in bone healing, we assessed bone healing in the Nf1(ob) (-/-) conditional mouse model lacking Nf1 specifically in osteoblasts. A closed distal tibia fracture protocol and a longitudinal study design were used. During the 21- to 28-day postfracture period, callus volume, as expected, decreased in wild-type but not in Nf1(ob) (-/-) mice, suggesting delayed healing. At these two time points, bone volume (BV/TV) and volumetric bone mineral density (vBMD) measured by 3D micro-computed tomography were decreased in Nf1(ob) (-/-) callus-bridging cortices and trabecular compartments compared with wild-type controls. Histomorphometric analyses revealed the presence of cartilaginous remnants, a high amount of osteoid, and increased osteoclast surfaces in Nf1(ob) (-/-) calluses 21 days after fracture, which was accompanied by increased expression of osteopontin, Rankl, and Tgfbeta. Callus strength measured by three-point bending 28 days after fracture was reduced in Nf1(ob) (-/-) versus wild-type calluses. Importantly, from a clinical point of view, this defect of callus maturation and strength could be ameliorated by local delivery of low-dose lovastatin microparticles, which successfully decreased osteoid volume and cartilaginous remnant number and increased callus BV/TV and strength in mutant mice. These results thus indicate that the dysfunctions caused by loss of Nf1 in osteoblasts impair callus maturation and weaken callus mechanical properties and suggest that local delivery of low-dose lovastatin may improve bone healing in NF1 patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.